Phase II Study of Paclitaxel, Ifosfamide, and Carboplatin in Pediatric Patients With Recurrent or Resistant Malignant Germ Cell Tumors
| Phase | Type | Status | Age | Sponsor |
|---|
| Phase II | Treatment | Active | Under 21 at original diagnosis | COG |
Outline
- This is a multicenter study.
- Patients receive paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1 and ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive filgrastim (G-CSF) subcutaneously or IV once daily until blood counts return to normal. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
- After completion of study treatment, patients are followed periodically for up to 5 years.
Objectives
Primary
- Determine the response rate in pediatric patients with recurrent or resistant malignant germ cell tumors treated with paclitaxel, ifosfamide, and carboplatin.
Secondary
- Determine the toxicity of this regimen in these patients.
Projected Accrual - A total of 20 patients will be accrued for this study.
Entry Criteria
Disease Characteristics:
- Histologically confirmed (at original diagnosis) extracranial germ cell tumor (GCT)
Containing 1 of the following malignant elements:
- Yolk sac tumor (endodermal sinus tumor)
- Choriocarcinoma
- Embryonal carcinoma
- Meets 1 of the following disease criteria:
- Recurrent malignant disease
- Chemotherapy-resistant disease
- Relapsed disease
- Disease refractory to conventional therapy
- Measurable disease
- Must have received a prior first-line chemotherapy regimen that included cisplatin
- Patients with tumor marker (AFP and/or BHCG) elevation alone or bone scan findings alone are not eligible*
- Patients with immature teratoma (any grade), germinoma, sex-cord stromal tumors, or recurrent GCT previously treated with surgery alone are not eligible
- Note: *Patients with measurable disease by imaging and elevated tumor markers do not require repeat biopsy for confirmation of recurrent disease; patients with imaging findings only (i.e., without concurrent elevation of tumor markers) require histologic confirmation of recurrence.
Age
- Under 21 at original diagnosis
Performance Status
- Karnofsky 50-100% (age > 16 years)
- Lansky 50-100% (age ≤ 16 years)
- ECOG 0-2
Life Expectancy
- Life expectancy ≥ 8 weeks
Hematopoietic
- Absolute neutrophil count ≥ 750/mm³
- Platelet count ≥ 75,000/mm³ (transfusion independent)
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- ALT < 2.5 times ULN for age
Renal
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR creatinine normal based on age/gender, as defined by the following:
- ≤ 0.4 mg/dL (1 month to < 6 months of age)
- ≤ 0.5 mg/dL (6 months to < 1 year of age)
- ≤ 0.6 mg/dL (1 to < 2 years of age)
- ≤ 0.8 mg/dL (2 to < 6 years of age)
- ≤ 1.0 mg/dL (6 to < 10 years of age)
- ≤ 1.2 mg/dL (10 to < 13 years of age)
- ≤ 1.4 mg/dL (13 to ≥ 16 years of age) (female)
- ≤ 1.5 mg/dL (13 to < 16 years of age) (male)
- ≤ 1.7 mg/dL (≥ 16 years of age) (male)
Cardiovascular
- Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by gated radionuclide study
Pulmonary
- No dyspnea at rest
- No exercise intolerance
- Pulse oximetry > 94% (if there is clinical indication for determination)
Other
- Patients with seizure disorder are eligible provided they are on non-enzyme inducing anticonvulsants and seizures are well controlled
- No CNS toxicity > grade 2
- No active graft-versus-host disease
- No allergy to Cremophor EL or castor oil
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
Prior / Concurrent Therapy:
Biologic Therapy
- See Disease Characteristics
- At least 1 week since prior growth factors (2 weeks for pegfilgrastim)
- At least 1 week since prior biologic therapy
Chemotherapy
- At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosourea)
- No other concurrent chemotherapy or immunomodulating agents
Endocrine therapy
Radiotherapy
- At least 2 weeks since prior local palliative radiotherapy (i.e., small port)
- At least 6 months since prior craniospinal radiotherapy or radiotherapy to ≥ 50% of
pelvis - At least 6 weeks since other prior substantial bone marrow radiotherapy
- Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable lesion is not irradiated
Surgery
Other
- At least 6 months since prior allogeneic stem cell transplantation
- Recovered from prior chemotherapy, immunotherapy, or radiotherapy
For more information, contact:
Rebecca Turner, MS, CCRP
Cincinnati Children's Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799
cancer@cchmc.org
